Navigation Links
Research could lead to way to halt deadly immune response
Date:2/9/2010

Researchers have teased out the molecular process that can shut down a marauding, often deadly immune response that kills thousands each year who suffer battlefield casualties, heart attacks, strokes, automobile accidents and oxygen deprivation, according to an article published in the January edition of Molecular Immunology.

The article provides additional detail about the enormously complex biomechanics of a reaction first observed in the lab by Neel Krishna, Ph.D., and Kenji Cunnion, M.D., while conducting pediatric research at Children's Hospital of The King's Daughters (CHKD) and Eastern Virginia Medical School (EVMS) in Norfolk, Va.

"Military medics and ER doctors know that one of the most common killers is an out-of-control immune system that destroys organs after a patient who has suffered a trauma is ostensibly stabilized," said Krishna, a pediatric virologist at CHKD and assistant professor of microbiology and molecular cell biology at EVMS.

The January publication comes almost four years after the two researchers made a serendipitous and unexpected finding when they inserted a shell of a virus that causes childhood diarrhea into a Petri dish primed to measure the response of primordial immune system.

The complement reaction completely stopped.

"Stopping this reaction pharmacologically could save lives on the battlefield, in hospital emergency rooms and in neonatal intensive care centers, where doctors struggle to save oxygen-deprived newborns," said Krishna. "Temporarily stopping the response could have a huge impact in trauma and save many lives."

Over the last four years, Krishna and Cunnion have successfully teased out the precise biological mechanism behind this unexpected response and identified the specific molecular region of the viral shell that stops the complement process.

One of the oldest biological mechanisms in the evolution of life, the complement system is so complex that research scientists spend entire careers studying it, publishing in journals devoted solely to the study of this primordial defense mechanism.

The complement system exists in almost identical form in everything from seagulls to starfish. Its job is to launch a massive, multi-pronged attack against any foreign body that could threaten the life or health of an organism. Each method of attack is instigated by molecular changes involving as many as 30 substances that result in the same effect, a component designed to destroy the membrane encasing offending cells.

In the case of trauma that leaves cells without oxygen for too long, the complement system kicks in when the re-oxygenation occurs and lays waste to partially damaged cells that might otherwise survive. This is known as a reperfusion injury. This process kills slowly, often over several days. In heart attacks, the death of heart cells, cardiomyocytes, during reperfusion is irreversible and lethal. In cases of trauma and hypoxia, the progressive death of brain cells often results in catastrophic, irreversible brain injury or death. Multiple organ dysfunction syndrome caused by reperfusion injury is the leading cause of death in surgical patients and in trauma patients who survive the first 24 hours.

For decades, researchers have worked to develop medications and treatments to mitigate the effects of reperfusion injury.

Stopping the complement cascade could eliminate the major cause. In earlier published research, authors showed that the introduction of the harmless membrane of the coat of human astrovirus, which causes pediatric diarrhea, shuts down the main pathway leading to activation of an often lethal complement cascade. The research published in January's Molecular Immunology, demonstrates that the introduction of the astrovirus shell also shuts down a second major trigger, dubbed the lectin pathway.

"This research explains the almost complete cessation of complement activity," Krishna said. "This rapid cessation can virtually eliminate most reperfusion injuries."

This research expands upon findings presented in September 2009 at the 12th European Meeting on Complement in Human Disease. That presentation drew enthusiatic response from a number of renowned complementologists who sought samples of the astrovirus shard used by Krishna and who intend to launch additional research into the phenomenon.

"We're rapidly moving toward therapeutic application," Krishna said.


'/>"/>

Contact: Doug Gardner
gardneda@evms.edu
757-446-6073
Eastern Virginia Medical School
Source:Eurekalert

Related biology news :

1. Research shows skeleton to be endocrine organ
2. Newly created cancer stem cells could aid breast cancer research
3. Dominant cholesterol-metabolism ideas challenged by new research
4. Researchers identify proteins involved in new neurodegenerative syndrome
5. Texas researchers and educators head for Antarctica
6. MGH researchers describe new way to identify, evolve novel enzymes
7. University of Pennsylvania researchers develop formula to gauge risk of disease clusters
8. University of Oregon researcher finds that on waters surface, nitric acid is not so tough
9. U of MN researchers discover noninvasive diagnostic tool for brain diseases
10. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
11. Story ideas from the Journal of Lipid Research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/3/2016)... , February 4, 2016 --> ... SEK 1,351.5 M (105.0), up 1,187% compared with fourth quarter of 2014. ... to SEK 517.6 M (loss: 30.0). Earnings per share increased ... was SEK 537.4 M (neg: 74.7). , ... Revenues amounted to SEK 2,900.5 M (233.6), up 1,142% compared with 2014. ...
(Date:2/2/2016)... NEW YORK , Feb. 2, 2016 ... healthcare facilities are primarily focused on medical ... that measure point-of-care parameters. Wearable devices that ... a user,s freedom of movement are being ... sensors for human biomedical signal acquisition coupled ...
(Date:2/2/2016)... 2, 2016   Parabon NanoLabs (Parabon) ... Army Research Office and the Defense Forensics and ... of the company,s Snapshot Kinship Inference ... more generally, defense-related DNA forensics.  Although Snapshot is ... appearance and ancestry from DNA evidence), it also ...
Breaking Biology News(10 mins):
(Date:2/5/2016)... 5, 2016 Australian-US drug discovery and development company, ... appointment of a new Chairman, Mr John O,Connor , ... immediately. James Garner , has also been ... former Acting CEO, Mr Iain Ross , will resume ... --> James Garner , has also been formally appointed ...
(Date:2/4/2016)... 4, 2016  Sangamo BioSciences, Inc. (NASDAQ: SGMO ... that Edward Lanphier , Sangamo,s president and chief ... of Sangamo,s ZFP Therapeutic ® development programs and ... pm ET on Thursday, February 11, 2016, at the ... The conference is being held in New ...
(Date:2/4/2016)... Beike Biotechnology, the Shenzhen ... ceremony in late 2015 to mark their successful combined ... --> --> The ... Cell Therapy" was hosted by the Shenzhen Cell Bank ... of Beike Biotechnology Co., Ltd. Shenzhen,s ...
(Date:2/4/2016)... 4, 2016 --> ... company is pleased to provide the following update on recent ... Over the last 3 months we have significantly increased our ... exceeding $1,000,000. As a result, we have positioned ourselves to ... license agreement and expect that development to continue on schedule. ...
Breaking Biology Technology: